Brain Tumor Biobank Development for Precision Medicine: Role of the Neurosurgeon

Abstract

Neuro-oncology biobanks are critical for the implementation of a precision medicine program. In this perspective, we review our first year experience of a brain tumor biobank with integrated next generation sequencing. From our experience, we describe the critical role of the neurosurgeon in diagnosis, research, and precision medicine efforts. In the first year of implementation of the biobank, 117 patients (Female: 62; Male: 55) had 125 brain tumor surgeries. 75% of patients had tumors biobanked, and 16% were of minority race/ethnicity. Tumors biobanked were as follows: diffuse gliomas (45%), brain metastases (29%), meningioma (21%), and other (5%). Among biobanked patients, 100% also had next generation sequencing. Eleven patients qualified for targeted therapy based on identification of actionable gene mutations. One patient with a hereditary cancer predisposition syndrome was also identified. An iterative quality improvement process was implemented to streamline the workflow between the operating room, pathology, and the research laboratory. Dedicated tumor bank personnel in the department of neurosurgery greatly improved standard operating procedure. Intraoperative selection and processing of tumor tissue by the neurosurgeon was integral to increasing success with cell culture assays. Currently, our institutional protocol integrates standard histopathological diagnosis, next generation sequencing, and functional assays on surgical specimens to develop precision medicine protocols for our patients. This perspective reviews the critical role of neurosurgeons in brain tumor biobank implementation and success as well as future directions for enhancing precision medicine efforts.

Keywords: biobank; brain tumor; neurosurgery; precision medicine; precision oncology.

Figure 1

Basic patient demographics from first year of brain tumor biobank experience. (A) Gender and age by decade of cohort. (B) Percent of Male and Female patients consented (C) Overall and (D) monthly percent patients undergoing tumor resection consented for tumor biobank. (E) Diagnostic classification of biobanked tumors. (F) Insurance status of biobanked patients. (G) Regional distribution of patients among Arkansas counties.

Figure 2

Role of the neurosurgeon in biobank for precision medicine. (A) Patient tumors with heterogenous regions are sent separately to pathology. Non-enhancing region corresponds with low grade histopathologic features. Enhancing region (<5% of tumor in this case) correlates with high grade histopathologic features. Arrow in the image shows calcification and the inset magnifies region of high proliferation with the arrow denoting cells undergoing cell division. (B) Pathologic tissue is sent for next generation sequencing. Heatmap of glioblastoma gene expression profiles stratified into classical, mesenchymal, neural and proneural subtypes. (C) Intraoperative tissue handling by the neurosurgeon involves regional harvesting utilizing MRI navigation (D) varied tumor extraction techniques such as non-thermal resection with specialized tools, and (E) intraoperative tissue processing with mechanical and chemical dissociation. (F) Once in the research laboratory, tissue can undergo single cell sequencing to determine heterogeneity. t-distributed stochastic neighbor embedding plots demonstrate differences between IDH mutant and IDH wildtype gliomas. (G) Tissue is also processed for patient derived models such as cell lines, organoids, and xenografts.